Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U44 Clinical Trial Optional)

The Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders is a funding opportunity offered by the National Institute of Neurological Disorders and Stroke (NINDS), under the National Institutes of Health (NIH), a federal agency within the U.S. Department of Health and Human Services. This opportunity is categorized under the U44 Small Business Innovation Research (SBIR) cooperative agreement and represents a reissue of PAR-21-059. It supports fast-track proposals for clinical validation of already-identified biomarker candidates aimed at neurological or neuromuscular disorders. This notice of funding opportunity (NOFO) seeks projects where candidate biomarkers have been identified and their detection methods analytically validated. The objective is to rigorously establish the clinical sensitivity, specificity, and overall utility of these biomarkers consistent with FDA guidance. The scope includes all neurological and neuromuscular conditions within the NINDS mission, across all ages. Proposals should target one or two well-defined context(s) of use and include evidence of prior testing in relevant clinical populations, analytical validation of the detection method, and justification of need. Clinical validation metrics such as sensitivity, specificity, ROC AUC, predictive values, and reference ranges are emphasized. Applicants must submit robust study designs, include a multi-site or well-justified single-site approach, and provide clear, quantitative milestones. Key evaluation factors include scientific rigor, study feasibility, context relevance, standardization of methods, and biological rationale. Applications should also include plans for sample/data sharing, intellectual property (if applicable), and multidisciplinary collaboration, including statisticians and regulatory experts. Budget consideration should incorporate costs for sharing analytic tools and methods as required by NIH reproducibility and transparency goals. Eligibility is limited to U.S.-based small business concerns, including those majority-owned by U.S. individuals or qualifying investment entities. Foreign entities are not eligible. Phase I budgets can request up to $700,000/year for up to 2 years, and Phase II up to $1.5 million/year for up to 3 years. Projects may be new, resubmissions, or revisions, and this NOFO accepts optional clinical trials. Multiple application cycles are available through June 2026, with a recurring annual schedule. Applications must follow NIH SBIR/STTR instructions and be submitted through the NIH ASSIST system or compatible platforms. Letters of intent are encouraged but not required, due 30 days before the chosen application deadline. Required registrations include SAM.gov, eRA Commons, Grants.gov, and SBA Company Registry. Applications must follow all NOFO and application guide instructions or risk disqualification. For pre-submission consultation, applicants are encouraged to contact Carol Taylor-Burds, PhD, at carol.taylor-burds@nih.gov or 301-496-1779. The program prioritizes biomarkers with strong biological rationale, unmet need alignment, and potential clinical utility, and it aims to support readiness for future FDA qualification pathways.